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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 27  |  Issue : 1  |  Page : 63-66

The role of immune restoration using highly active antiretroviral therapy in the management of AIDS-related Kaposi's sarcoma coexisting with pulmonary tuberculosis


1 Department of Medicine, Dermatology Unit, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
2 Department of Medicine, Infectious Disease Unit, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Date of Submission10-Jul-2019
Date of Acceptance18-Dec-2019
Date of Web Publication14-Jan-2020

Correspondence Address:
Dr. Umar Abdullahi
Department of Medicine, Dermatology Unit, Ahmadu Bello University Teaching Hospital, Zaria
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/npmj.npmj_102_19

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  Abstract 


A 35-year-old highly active antiretroviral therapy (HAART)-naïve woman diagnosed 2 years earlier presented with complaints of cough, fever and progressive weight loss of 5 months and skin rashes of 2 months. Clinical examination revealed a chronically ill-looking young woman who was wasted and pale, with purplish flat-topped papules and nodules on the skin of her neck, trunk, forearms and thighs. She also had a single lesion on the hard palate. Chest examination shows reduced breath sounds with crepitations. Sputum acid-fast bacilli were positive, and skin biopsy taken for histology confirmed Kaposi's sarcoma (KS). The patient recovered fully on antiretroviral and antituberculosis therapy without the need for any specific chemotherapy for KS. We report this case to elucidate the role of immune reconstitution as a treatment modality for AIDS-related KS, as well as to point out the possibility of multiple opportunistic conditions coexisting amongst patients with advanced HIV disease.

Keywords: Advanced HIV disease, AIDS-related Kaposi's sarcoma, highly active antiretroviral therapy naïve, multiple opportunistic conditions, non-nucleoside reverse transcriptase inhibitor-based regimens, tuberculosis


How to cite this article:
Abdullahi U, Adeiza MA. The role of immune restoration using highly active antiretroviral therapy in the management of AIDS-related Kaposi's sarcoma coexisting with pulmonary tuberculosis. Niger Postgrad Med J 2020;27:63-6

How to cite this URL:
Abdullahi U, Adeiza MA. The role of immune restoration using highly active antiretroviral therapy in the management of AIDS-related Kaposi's sarcoma coexisting with pulmonary tuberculosis. Niger Postgrad Med J [serial online] 2020 [cited 2020 Jan 21];27:63-6. Available from: http://www.npmj.org/text.asp?2020/27/1/63/275802




  Introduction Top


Kaposi's sarcoma (KS) is a malignant tumour originating from the vascular endothelium and was first described by Moritz Kohn in 1872.[1] It is the most common malignancy seen in individuals living with HIV/AIDS that causes significant morbidity and mortality.[2] The incidence of this condition is on the decline as a result of introduction and wide use of highly active antiretroviral therapy (HAART).[2] These drugs have been shown to improve morbidity and mortality amongst HIV/AIDS patients with KS.[2] Furthermore, the use of HAART alone has been employed to treat AIDS-KS without the need for KS-specific chemotherapy.[3] Tuberculosis (TB) still remains the most prevalent opportunistic infection amongst individuals with HIV infection and a major cause of HIV-related dead in resource-poor settings.[4] HAART has been shown to improve survival amongst patients with HIV/TB coinfection.[4] Few cases of KS in TB patients have been reported in the medical literature, with some reporting KS as a complication of poorly managed chronic TB.[5] However, it usually exists as a concomitant opportunistic infection in patients with advanced HIV infection.[5] We report this case to elucidate the role of immune restoration using HAART and anti-TB drugs in the management of AIDS-related KS, to achieve complete remission of KS without recourse to cytotoxic chemotherapy, as well as pointing out the possibility of multiple concomitant opportunistic conditions that may present amongst patients with advanced HIV disease.


  Case Report Top


A 35-year-old nurse who was diagnosed HIV positive in March 2014 but had never been on HAART and resorting to alternative/traditional medications presented to the HIV treatment and care centre of Ahmadu Bello University Teaching Hospital, Zaria, Nigeria, in May 2016 with complaints of cough, fever and progressive weight loss of 5-month duration and skin rashes of 2 months. Cough was productive of whitish mucoid sputum with no haemoptysis and chest pain; she had dyspnoea on exertion, but there was no orthopnoea, paroxysmal nocturnal dyspnoea and leg swelling. There was an associated low-grade intermittent fever with drenching night sweat. There was a positive history of contact with an open pulmonary TB case, and she had lost weight significantly since the onset of her symptoms. Two months before the presentation, she had noticed dark-coloured rashes on her trunk, neck and extremities which were slightly raised, painless, non-itchy and not ulcerating. There was no dysphagia, odynophagia, diarrhoea, haematemesis, passage of melena stools or haematochezia and no history of yellowish discolouration of her eyes. Reviews of central nervous and genitourinary systems were essentially unremarkable.

She was not previously known to be hypertensive, diabetic or asthmatic. She did not smoke cigarette or ingest alcohol. She had a past history of multiple high-risk sexual exposures and did not use protection. She had lost her husband 9 years previously in a road traffic accident.

Clinical examination revealed a chronically ill-looking young woman, febrile with a temperature of 37.5°C, wasted and pale with generalised peripheral lymphadenopathy involving both the axillary and cervical groups of lymph nodes, largest measuring 3 cm by 3 cm in the right axilla, non-tender, firm and freely mobile. Skin examination revealed dark dusky violaceous papules, plaques and nodules on the neck, forearms, trunk and thighs as well as on the hard palate [Figure 1] and [Figure 2]. Skin lesions were indurated and displayed a mild peau d'orange changes. There were no associated genital lesions. Chest examination revealed tachypnoea with reduced vesicular breath sounds and widespread coarse crepitations. She was tachycardic but had a normal blood pressure and normal heart sounds. There were no abdominal masses, and examination of the other systems was essentially normal. An impression of Stage 4 HIV with disseminated AIDS-related KS was made to rule out pulmonary TB.
Figure 1: Biopsy site and dark purplish raised Kaposi's sarcoma lesions at the back of the neck and shoulder

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Figure 2: Multiple Kaposi's sarcoma lesions on the lower limb

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From the available results, chest X-ray showed widespread non-homogenous opacities on reticulonodular background in both lung fields with bilateral hilar fullness, loss of left lung volume and tenting of the right hemidiaphragm [Figure 3]. Erythrocyte sedimentation rate was 100 mm/h, packed cell volume of 32%, white cell count of 10.8 × 109/L with neutrophils constituting 72%, eosinophils 3% and lymphocytes 25%. Serum electrolytes and liver function tests were all normal except for hyperuricaemia and hypocalcaemia. Her baseline CD4 T-lymphocyte count on presentation was 122 cell/μl. Mantoux test was strongly positive (14 mm); sputum examination for acid-fast bacilli (AFB) was positive in two of the three samples. Sputum GeneXpert and culture for Mycobacterium tuberculosis were not done. Skin biopsy taken for histology showed a dermal lesion composed of plump of spindle cells in sheets, with multiple slit-like vascular channels containing red blood cells [Figure 4]. Admixed with these are lymphocytes and plasma cells. The overall features are those of KS.
Figure 3: Chest X-ray showing widespread reticulonodular infiltrates with hilar fullness, tenting of left hemidiaphragm and loss of lung volume on the left hilar fullness, tenting of left hemidiaphragm and loss of lung volume on the left

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Figure 4: Proliferating vascular channels containing red cells and aborted binumerous spindle cells arranged with lymphocytic infiltrations (×200)

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An assessment of Stage 4 HIV was made with disseminated KS (AIDS Clinical Trial Group [ACTG] KS Stage T1, I1 and S1 [poor risk]), coexisting with smear-positive pulmonary TB.

She was commenced on rifampicin-based four-drug anti-TB intensive phase therapy (rifampicin/isoniazid/pyrazinamide/ethambutol) 1 week after her presentation. The patient subsequently was commenced on emtricitabine/ efferverenze/tenofovir (a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART) 2 weeks after commencing the anti-TB therapy and was followed up closely for clinical improvement, drug side effect and interaction.

A month after anti-TB therapy was commenced, the fever and cough had resolved and she had started gaining weight. She was sputum AFB negative at 2-month and 5-month follow-up after the commencement of anti-TB; a repeat CD4 cell count and viral load at 6 months post-HAART were 540 cells/mm3 and <20 copies/ml, respectively. The KS lesions as well as the lymphadenopathy resolved completely after completing the anti-TB therapy at 6 months without the need for any KS-specific cytotoxic chemotherapy. The patient is currently doing well and on her routine follow-up in the HIV treatment and care centre on HAART.


  Discussion Top


KS remains the most common malignancy seen in patients with HIV/AIDS since after the first case was described by Friedman-Kien et al. in 1981 amongst young homosexual men.[6] This tumour was reported to be 200,000 times more frequent in HIV-infected persons compared to the general population before the introduction of HAART.[7] However, the incidence is on the decline following the introduction and wide use of HAART.[2]

This case report highlighted the role of immune restoration using HAART in the management of AIDS-related KS. The use of HAART alone has been employed in the treatment of AIDS-related KS.[3] These improved outcomes have been widely attributed to immune restoration and virologic suppression after the use of HAART.[3] However, the HAART combination with protease inhibitors (PIs) and reverse-transcriptase inhibitors has been shown to be more effective in preventing HIV/AIDS-associated opportunistic infections.[8] Studies have shown that some PIs such as ritonavir, saquinavir, nelfinavir and indinavir can slow down the development and progression of KS by inhibiting angiogenesis, tumour growth and also inhibiting replication of KS-associated herpesvirus 8 (HHV-8).[3] All these factors contribute towards the resolution of KS observed in patients on HAART.

The index case is a 35-year-old woman who was initially diagnosed HIV positive 2 years previously but then lost to follow-up without being commenced on HAART, and she resorted to alternative/traditional medications. She subsequently presented with multiple opportunistic infections that include disseminated KS and smear-positive pulmonary TB; all these are as a result of loss to follow-up, progressive immunosuppression and delay in commencing HAART. She was subsequently evaluated and commenced on anti-TB medications and then on HAART, with complete regression of all the KS lesions without the need for KS-specific therapy, even though she has a disseminated disease. This has clearly elucidated the role of immune restoration using HAART in the management of AIDS-related KS. Majority of case reports that described the role of HAART as monotherapy for KS actually involved localised KS lesions not disseminated disease as in the index case.

Many studies have attributed several factors that contribute towards the resolution of AIDS-related KS lesions following the use of PI-based HAART alone, and these include decreased HIV-Tat protein production, regulation of cytokine production, improved immunity against HHV-8 and the antiproliferative/antiangiogenic effects.[9] However, some studies have observed a much lower incidence of KS in HIV-infected patients receiving NNRTI-based regimen as compared to those on a PI-based regimen.[2] Thus, NNRTIs are also as effective as PIs in managing patients with AIDS-related KS with better patient compliance and fewer side effects.[2] Thus, the non-PI-based regimens are as effective as the PI-based regimens to induce remission of KS.[2] The index case was not placed on the PI-based regimen because of concomitant use of rifampicin-based anti-TB to prevent the microsomal enzyme induction of PI and the attendant risk of treatment failure, even though studies have suggested it as the preferred choice for AIDS-related KS.[9] However, the NNRTI-based regimen produced good clinical outcome and tolerability.

This case report again confirms the efficacy of NNRTI-based regimen and also reaffirms the view that the regression of AIDS-related KS following the use of HAART is related to immune restoration and virological suppression, not really a result of antiangiogenic/antiproliferative effect of HAART. There have been conflicting results concerning the role played by increased CD4 T-lymphocyte count on KS outcome and the role played by virological suppression. Some studies have shown a high CD4 T-lymphocyte count to be positively correlated with KS remission.[8],[10] In contrast, some studies had suggested virological suppression as the major predictor of AIDS-related KS remission irrespective of immune restoration.[9] The KS regression observed in the index case is related to an overall immune restoration and virological suppression, rather than by a direct specific antitumour effect of HAART.

The response of KS lesion to HAART may depend on the clinical stage of the disease based on ACTG stage, with patients in ACTG KS stage S0 before HAART more likely to have remission of KS lesions within the first 6 months of treatment with HAART alone.[9] This patient even though she was classified as ACTG KS Stage T1, I1 and S1 (poor risk), which ideally should have been treated with KS-specific chemotherapy in addition to HAART,[2] responded to HAART alone.

Finally, there are few reported cases of KS coexisting with TB in the medical literature, and some reported KS as a complication of long-standing and neglected TB. However, it may be concomitant opportunistic conditions that may present amongst patients with advanced HIV/AIDS as seen with the index case.


  Conclusion Top


AIDS-related KS can completely regress following immune restoration using HAART without the need for KS-specific chemotherapy. Immune restoration as well as virologic suppression by HAART appears to be the major factor in causing regression of KS lesions. NNRTI-based regimens are equally effective as PI-based regimens in giving good clinical outcome in HIV-infected patients with KS.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Acknowledgement

We wish to express our sincere appreciation to our client for willingly allowing us to use his pictures for this case report.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kaposi M. Idiopathic multiple pigmented lesions of the skin. Arch Dermatol Syph 1872;4:265-73.  Back to cited text no. 1
    
2.
Bower M, Weir J, Francis N, Newsom-Davis T, Powles S, Crook T, et al. The effect of HAART in 254 consecutive patients with AIDS-related Kaposi's sarcoma. AIDS 2009;23:1701-6.  Back to cited text no. 2
    
3.
Kowalkowski MA, Kramer JR, Richardson PR, Suteria I, Chiao EY. Use of boosted protease inhibitors reduces Kaposi sarcoma incidence among male veterans with HIV infection. Clin Infect Dis 2015;60:1405-14.  Back to cited text no. 3
    
4.
Manosuthi W, Wiboonchutikul S, Sungkanuparph S. Integrated therapy for HIV and tuberculosis. AIDS Res Ther 2016;13:22.  Back to cited text no. 4
    
5.
Virgil P, Ana MP, Florentina D. Unilateral Kaposi sarcoma in a patient with pulmonary tuberculosis and history of breast neoplasm. Roman J Clin Exp Dermatol 2015;2:100-03.  Back to cited text no. 5
    
6.
Friedman-Kien AE, Laubenstein LJ, Rubinstein P, Buimovici-Klein E, Marmor M, Stahl R, et al. Disseminated Kaposi's sarcoma in homosexual men. Ann Intern Med 1982;96:693-700.  Back to cited text no. 6
    
7.
Engels EA, Pfeiffer RM, Goedert JJ, Virgo P, McNeel TS, Scoppa SM, et al. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS 2006;20:1645-54.  Back to cited text no. 7
    
8.
Lebbé C, Blum L, Pellet C, Blanchard G, Vérola O, Morel P, et al. Clinical and biological impact of antiretroviral therapy with protease inhibitors on HIV-related Kaposi's sarcoma. AIDS 1998;12:45-9.  Back to cited text no. 8
    
9.
Martinez V, Caumes E, Gambotti L, Ittah H, Morini JP, Deleuze J, et al. Remission from Kaposi's sarcoma on HAART is associated with suppression of HIV replication and is independent of protease inhibitor therapy. Br J Cancer 2006;94:1000-6.  Back to cited text no. 9
    
10.
Autran B, Carcelain G, Li TS, Blanc C, Mathez D, Tubiana R, et al. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 1997;277:112-6.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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